Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.

* This is a professional Version *

Overview of Platelet Disorders

by David J. Kuter, MD, DPhil

Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes, which in turn shed platelets from their cytoplasm. Thrombopoietin is produced in the liver at a constant rate and its circulating level is determined by the extent to which circulating platelets are cleared, and possibly by bone marrow megakaryocytes. Platelets circulate for 7 to 10 days. About one third are always transiently sequestered in the spleen. The platelet count is normally 140,000 to 440,000/μL. However, the count can vary slightly according to menstrual cycle phase, decrease during near-term pregnancy (gestational thrombocytopenia), and increase in response to inflammatory cytokines (secondary, or reactive, thrombocytosis). Platelets are eventually destroyed by apoptosis, a process independent of the spleen.

Platelet disorders include

  • An abnormal increase in platelets (thrombocythemia and reactive thrombocytosis )

  • A decrease in platelets (thrombocytopenia)

  • Platelet dysfunction

Any of these conditions, even those in which platelets are increased, may cause defective formation of hemostatic plugs and bleeding.

The risk of bleeding is inversely proportional to the platelet count and platelet function (see Table: Platelet Count and Bleeding Risk). When platelet function is reduced (eg, as a result of uremia or aspirin use), the risk of bleeding increases.

Platelet Count and Bleeding Risk

Platelet Count

Risk of Bleeding*

≥ 50,000/μL

Minimal

20,000–50,000/μL

Minor bleeding after trauma

< 20,000/μL

Spontaneous bleeding

< 5000/μL

Severe, possibly life-threatening spontaneous bleeding

*Reduced platelet function (eg, due to uremia or aspirin use) adds to risk of bleeding in each platelet count range.

Etiology

Thrombocythemia and thrombocytosis

Essential thrombocythemia is a myeloproliferative disorder (see Essential Thrombocythemia) involving overproduction of platelets because of a clonal abnormality of a hematopoietic stem cell. A markedly elevated platelet count is typically associated with thrombosis, but some patients develop bleeding.

Reactive thrombocytosis (see Reactive Thrombocytosis (Secondary Thrombocythemia)) is platelet overproduction in response to another disorder. There are many causes, including acute infection, chronic inflammatory disorders (eg, RA, inflammatory bowel disease, TB, sarcoidosis), iron deficiency, and certain cancers. Reactive thrombocytosis is not typically associated with an increased risk of thrombosis.

Thrombocytopenia

Causes of thrombocytopenia can be classified by mechanism (see Table: Classification of Thrombocytopenia) and include decreased platelet production, increased splenic sequestration of platelets with normal platelet survival, increased platelet destruction or consumption (both immunologic and nonimmunologic causes), dilution of platelets, and a combination of these mechanisms.

Increased splenic sequestration is suggested by splenomegaly.

A large number of drugs may cause thrombocytopenia (see Drug-induced immunologic destruction), typically by triggering immunologic destruction.

Overall, the most common specific causes of thrombocytopenia include

  • Gestational thrombocytopenia

  • Drug-induced thrombocytopenia due to immune-mediated platelet destruction (commonly, heparin, trimethoprim/sulfamethoxazole)

  • Drug-induced thrombocytopenia due to dose-dependent bone marrow suppression (eg, chemotherapeutic agents)

  • Thrombocytopenia accompanying systemic infection

  • Immune thrombocytopenia (ITP, formerly called immune thrombocytopenic purpura)

Platelet dysfunction

Platelet dysfunction may stem from an intrinsic platelet defect or from an extrinsic factor that alters the function of normal platelets. Dysfunction may be hereditary or acquired. Hereditary disorders of platelet function consist of von Willebrand disease, the most common hereditary hemorrhagic disease, and hereditary intrinsic platelet disorders (see Hereditary Intrinsic Platelet Disorders), which are much less common. Acquired disorders of platelet function (see Acquired Platelet Dysfunction) are commonly due to diseases (eg, renal failure) as well as to aspirin and other drugs.

Classification of Thrombocytopenia

Cause

Conditions

Diminished or absent megakaryocytes in bone marrow

Aplastic anemia

Leukemia

Myelosuppressive drugs (eg, hydroxyurea, interferon alfa-2b, chemotherapy drugs)

Paroxysmal nocturnal hemoglobinuria (some patients)

Diminished platelet production despite the presence of megakaryocytes in bone marrow

Alcohol-induced thrombocytopenia

Bortezomib use

HIV-associated thrombocytopenia

Myelodysplastic syndromes (some)

Vitamin B 12 or folate (folic acid) deficiency

Platelet sequestration in enlarged spleen

Cirrhosis with congestive splenomegaly

Gaucher disease

Myelofibrosis with myeloid metaplasia

Immunologic destruction

Connective tissue disorders

Drug-induced thrombocytopenia

HIV-associated thrombocytopenia

Immune thrombocytopenia

Lymphoproliferative disorders

Neonatal alloimmune thrombocytopenia

Posttransfusion purpura

Nonimmunologic destruction

Certain systemic infections (eg, hepatitis, Epstein-Barr virus, cytomegalovirus, or dengue virus infection)

Disseminated intravascular coagulation

Pregnancy (gestational thrombocytopenia)

Sepsis

Thrombocytopenia in acute respiratory distress syndrome

Thrombotic thrombocytopenic purpura–hemolytic-uremic syndrome

Dilution

Massive RBC replacement or exchange transfusion (most RBC transfusions use stored RBCs that do not contain many viable platelets)

Symptoms and Signs

Platelet disorders result in a typical pattern of bleeding:

  • Multiple petechiae in the skin (typically most evident on the lower legs)

  • Scattered small ecchymoses at sites of minor trauma

  • Mucosal bleeding (oropharyngeal, nasal, GI, GU)

  • Excessive bleeding after surgery

Heavy GI bleeding and bleeding into the CNS may be life threatening. However, bleeding into tissues (eg, deep visceral hematomas or hemarthroses) rarely occurs with thrombocytopenia, which causes immediate, superficial bleeding following an injury. Bleeding into the tissues (often delayed for up to a day after trauma) suggests a coagulation disorder (eg, hemophilia).

Diagnosis

  • Clinical presentation of petechiae and mucosal bleeding

  • CBC with platelets, coagulation studies, peripheral blood smear

  • Sometimes bone marrow aspiration

  • Sometimes von Willebrand antigen and factor activity studies

Platelet disorders are suspected in patients with petechiae and mucosal bleeding. A CBC with platelet count, coagulation studies, and a peripheral blood smear are obtained. Excessive platelets and thrombocytopenia are diagnosed based on the platelet count; coagulation studies are normal unless there is a simultaneous coagulopathy. In patients with a normal CBC, platelet count, INR, and PTT, platelet dysfunction is suspected.

Pearls & Pitfalls

  • Suspect platelet dysfunction in patients with petechiae and/or hemorrhage but with normal platelet count and coagulation test results.

Thrombocytopenia

In patients with thrombocytopenia, the peripheral smear may suggest the cause (see Table: Peripheral Blood Findings in Thrombocytopenic Disorders). If the smear shows abnormalities other than thrombocytopenia, such as nucleated RBCs or abnormal or immature WBCs, bone marrow aspiration is indicated. Bone marrow aspiration reveals the number and appearance of megakaryocytes and is the definitive test for many disorders causing bone marrow failure. However, normal number and appearance of megakaryocytes does not always indicate normal platelet production. For example, in patients with immune thrombocytopenia, platelet production may be decreased despite the normal appearance and increased number of megakaryocytes. If the bone marrow is normal but the spleen is enlarged, increased splenic sequestration is the likely cause of thrombocytopenia. If the bone marrow is normal and the spleen is not enlarged, excess platelet destruction is the likely cause. Measurement of antiplatelet antibodies is not clinically useful. HIV testing is done in patients at risk of HIV infection. Bone marrow examination is rarely required in patients who present with typical features of ITP.

Peripheral Blood Findings in Thrombocytopenic Disorders

Findings

Conditions

Normal RBCs and WBCs

Drug-induced thrombocytopenia

Gestational thrombocytopenia

HIV-related thrombocytopenia

Immune thrombocytopenia

Posttransfusion purpura

RBC fragmentation (schistocytes)

Metastatic cancer

DIC

Preeclampsia with DIC

Thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome

WBC abnormalities

Hypersegmented polymorphonuclear leukocytes in megaloblastic anemias

Immature cells or increased mature lymphocytes in leukemia

Markedly diminished granulocytes in aplastic anemia

Frequent giant platelets (approaching the size of RBCs)

Bernard-Soulier syndrome

Disorders related to the myosin, heavy chain 9, non-muscle gene ( MYH9 )

Other congenital thrombocytopenias

RBC abnormalities, nucleated RBCs, and immature granulocytes

Myelodysplasia

DIC = disseminated intravascular coagulation.

Suspected platelet dysfunction

In patients with platelet dysfunction, a drug cause is suspected if symptoms began only after the patient started taking a potentially causative drug (eg clopidogrel, ticagrelor). Platelet dysfunction caused by drugs may be severe, but specialized tests are rarely needed. A hereditary cause is suspected if there is a lifelong history of easy bruising; bleeding after tooth extractions, surgery, childbirth, or circumcision; or heavy menstruation. In the case of a suspected hereditary cause, von Willebrand factor (VWF) antigen and VWF activity studies are routinely done. In some patients, platelet aggregation tests may identify a defect in how the platelet responds to various platelet agonists ( adenosine diphosphate [ADP], collagen, thrombin) and thereby demonstrate the type of platelet defect. Platelet dysfunction caused by systemic disorders is typically mild and of minor clinical importance. In these patients, the causative systemic disorder is the clinical concern, and hematologic tests are unnecessary.

Treatment

  • Stopping drugs that impair platelet function

  • Rarely platelet transfusions

In patients with thrombocytopenia or platelet dysfunction, drugs that further impair platelet function, particularly aspirin and other NSAIDs, should not be given. Patients who are already taking such drugs should consider alternative drugs, such as acetaminophen, or simply stop using them.

Patients may require platelet transfusion, but transfusions are given only in limited situations (see Platelets). Prophylactic transfusions are used sparingly because they may lose their effectiveness with repeated use due to the development of platelet alloantibodies. In platelet dysfunction or thrombocytopenia caused by decreased production, transfusions are reserved for patients with active bleeding, severe thrombocytopenia (eg, platelet count < 10,000/μL), or in need of invasive procedures. In thrombocytopenia caused by platelet destruction, transfusions are reserved for life-threatening or CNS bleeding.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • No US brand name
  • PANHEPRIN
  • VELCADE
  • HYDREA
  • ADENOCARD
  • PLAVIX
  • BRILINTA
  • TYLENOL

* This is a professional Version *